Final results of a phase 1 trial with soquelitinib (SQL), a selective interleukin-2-inducible T cell kinase (ITK) inhibitor for treatment of relapsed/refractory (R/R) T cell lymphomas (TCL)

作者：Richard A. Miller, Ryan A. Wilcox, John Reneau, Costas K. Yannakou, Won Seog Kim, Tatyana Feldman, Y. H. Kim, Michael S. Khodadoust, Dejan Radeski, Robin Gasiorowski, Dok Hyun Yoon, Yuqin Song, Andrew Hotson, Suresh Mahabhashyam · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-778 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Lymphoma Diagnosis and Treatment、Histone Deacetylase Inhibitors Research

Abstract Introduction ITK is expressed in T cells and NK cells and is involved in multiple signaling pathways including T cell receptor (TCR) activation and differentiation of T helper (Th) cells. In mice, gene knock-out of ITK leads to Th1 skewing of Th cells. SQL is an oral, covalent inhibitor of ITK that suppresses Th2 response with sparing of Th1 function and cytokine production (Hsu et al. npj Drug Discov, 2024). In vivo studies in murine tumor models have demonstrated anti-tumor activity in several tumor types including tumors that do not express ITK. These studies demonstrated increased infiltration of normal CD8+ T cells with enhanced cytolytic capacity based on elevated production of IFNγ and TNFα. Tonic TCR signaling has been implicated in TCL, and ITK inhibition with SQL was found to reduce GATA3 expression (master transcriptional regulator of Th2), which is ITK dependent (Geng et al. Blood Cancer J, 2022). GATA3+ subtype of peripheral TCL is associated with a poor prognosis; median overall survival (OS) <1 year (Amador et al. Blood, 2019). We hypothesized that SQL would be active in TCL due to direct effects on tumor cells as well as induction of anti-tumor immunity. We now report the results of a Phase 1 dose escalation trial in R/R TCL (NCT03952078). Methods Twenty-eight patients (pts) were enrolled in the dose escalation portion of the trial evaluating 100, 200, 400 and 600mg oral BID until tumor progression. ITK target occupancy was measured in blood T ...